The River Orontes in Syria and Turkey: downstream variation of fluvial archives in different crustal blocks

The geomorphology and Quaternary history of the River Orontes in western Syria and south-central Turkey have been studied using a combination of methods: field survey, differential GPS, satellite imagery, analysis of sediments to determine provenance, flow direction and fluvial environment, incorporation of evidence from fossils for both palaeoenvironments and biostratigraphy, uranium-series dating of calcrete cement, reconciliation of Palaeolithic archaeological contents, and uplift modelling based on terrace height distribution. The results underline the contrasting nature of different reaches of the Orontes, in part reflecting different crustal blocks, with different histories of landscape evolution. Upstream from Homs the Orontes has a system of calcreted terraces that form a staircase extending to ~200 m above the river. New U-series dating provides an age constraint within the lower part of the sequence that suggests underestimation of terrace ages in previous reviews. This upper valley is separated from another terraced reach, in the Middle Orontes, by a gorge cut through the Late Miocene–Early Pliocene Homs Basalt. The Middle Orontes terraces have long been recognized as a source of mammalian fossils and Palaeolithic artefacts, particularly from Latamneh, near the downstream end of the reach. This terraced section of the valley ends at a fault scarp, marking the edge of the subsiding Ghab Basin (a segment of the Dead Sea Fault Zone), which has been filled to a depth of ~ 1 km by dominantly lacustrine sediments of Pliocene–Quaternary age. Review of the fauna from Latamneh suggests that its age is 1.2–0.9 Ma, significantly older than previously supposed, and commensurate with less uplift in this reach than both the Upper and Lower Orontes. Two localities near the downstream end of the Ghab have provided molluscan and ostracod assemblages that record somewhat saline environments, perhaps caused by desiccation within the former lacustrine basin, although they include fluvial elements. The Ghab is separated from another subsiding and formerly lacustrine depocentre, the Amik Basin of Hatay Province, Turkey, by a second gorge, implicit of uplift, this time cut through Palaeogene limestone. The NE–SW oriented lowermost reach of the Orontes is again terraced, with a third and most dramatic gorge through the northern edge of the Ziyaret Dağı mountains, which are known to have experienced rapid uplift, probably again enhanced by movement on an active fault. Indeed, a conclusion of the research, in which these various reaches are compared, is that the crust in the Hatay region is significantly more dynamic than that further upstream, where uplift has been less rapid and less continuous

Poly(amidoamine)s synthesis, characterisation and interaction with BSA

Cationic poly(amidoamine)s (PAAs) were synthesised and characterised by NMR and gel permeation chromatography. Their thermal properties were investigated using thermogravimetric analysis and differential scanning calorimetry. Although poly(amidoamine)s have been used as endosomolytic polymers for protein intracellular delivery, the interaction of the polymers with the proteins still need to be investigated. BSA was used as a model protein and complexation with the different poly(amidoamine) s was investigated using gel retardation assays, fluorescence spectroscopy and high sensitivity differential scanning calorimetry. Our results indicate that the thermal stability of BSA was affected upon interaction and complexation with the poly(amidoamine)s, however these interactions did not seem to modify the structure of the protein. Polymer flexibility seemed to favour polymer/protein complexation and promoted thermal stability

Multiple Scale Reorganization of Electrostatic Complexes of PolyStyrene Sulfonate and Lysozyme

We report on a SANS investigation into the potential for these structural reorganization of complexes composed of lysozyme and small PSS chains of opposite charge if the physicochemical conditions of the solutions are changed after their formation. Mixtures of solutions of lysozyme and PSS with high matter content and with an introduced charge ratio [-]/[+]intro close to the electrostatic stoichiometry, lead to suspensions that are macroscopically stable. They are composed at local scale of dense globular primary complexes of radius ~ 100 {\AA}; at a higher scale they are organized fractally with a dimension 2.1. We first show that the dilution of the solution of complexes, all other physicochemical parameters remaining constant, induces a macroscopic destabilization of the solutions but does not modify the structure of the complexes at submicronic scales. This suggests that the colloidal stability of the complexes can be explained by the interlocking of the fractal aggregates in a network at high concentration: dilution does not break the local aggregate structure but it does destroy the network. We show, secondly, that the addition of salt does not change the almost frozen inner structure of the cores of the primary complexes, although it does encourage growth of the complexes; these coalesce into larger complexes as salt has partially screened the electrostatic repulsions between two primary complexes. These larger primary complexes remain aggregated with a fractal dimension of 2.1. Thirdly, we show that the addition of PSS chains up to [-]/[+]intro ~ 20, after the formation of the primary complex with a [-]/[+]intro close to 1, only slightly changes the inner structure of the primary complexes. Moreover, in contrast to the synthesis achieved in the one-step mixing procedure where the proteins are unfolded for a range of [-]/[+]intro, the native conformation of the proteins is preserved inside the frozen core

Human Galectins Induce Conversion of Dermal Fibroblasts into Myofibroblasts and Production of Extracellular Matrix: Potential Application in Tissue Engineering and Wound Repair

Members of the galectin family of endogenous lectins are potent adhesion/growth-regulatory effectors. Their multi-functionality opens possibilities for their use in bioapplications. We studied whether human galectins induce the conversion of human dermal fibroblasts into myofibroblasts (MFBs) and the production of a bioactive extracellular matrix scaffold is suitable for cell culture. Testing a panel of galectins of all three subgroups, including natural and engineered variants, we detected activity for the proto-type galectin-1 and galectin-7, the chimera-type galectin-3 and the tandem-repeat-type galectin-4. The activity of galectin-1 required the integrity of the carbohydrate recognition domain. It was independent of the presence of TGF-beta 1, but it yielded an additive effect. The resulting MFBs, relevant, for example, for tumor progression, generated a matrix scaffold rich in fibronectin and galectin-1 that supported keratinocyte culture without feeder cells. Of note, keratinocytes cultured on this substratum presented a stem-like cell phenotype with small size and keratin-19 expression. In vivo in rats, galectin-1 had a positive effect on skin wound closure 21 days after surgery. In conclusion, we describe the differential potential of certain human galectins to induce the conversion of dermal fibroblasts into MFBs and the generation of a bioactive cell culture substratum. Copyright (C) 2011 S. Karger AG, Base

Cribriform architecture outperforms Gleason pattern 4 percentage and tertiary Gleason pattern 5 in predicting the outcome of Grade Group 2 prostate cancer patients

Aims Gleason pattern 4 (GP4) percentage, invasive cribriform and/or intraductal carcinoma (IC/IDC) and the presence of tertiary Gleason pattern 5 (TP5) in radical prostatectomy (RP) specimens all aid in the risk stratification of Grade Group (GG) 2 prostate cancer patients. However, it is unclear to what extent these pathological features are mutually related and what are their individual values if they are investigated simultaneously. The aims of this study were: (i) to determine the mutual relationships of the GP4 percentage, IC/IDC and TP5 in GG2 RP specimens; and (ii) to assess their prognostic value for biochemical recurrence-free survival (BCRFS). Methods and results Of 1064 RP specimens, 472 (44.4%) showed GG2 prostate cancer. Patients with >= 25% GP4 more frequently had IC/IDC (67.0% versus 43.9%; P = 25%) GP4 percentage (P = 0.10) were not. In multivariable analysis, IC/IDC was an independent prognostic factor (HR 1.9; 95% CI 1.2-2.9; P = 0.005) for BCRFS, whereas a continuous or dichotomised GP4 percentage and TP5 were not independent prognostic factors. Conclusion In conclusion, a higher GP4 percentage in RP specimens was associated with more frequent IC/IDC and TP5. IC/IDC was an independent predictor for BCRFS, whereas the GP4 percentage and TP5 were not. These findings underscore the importance of routinely including the presence of IC/IDC in RP pathology reports.Prostatic carcinom

Autosomal dominant polycystic kidney disease with diffuse proliferative glomerulonephritis - an unusual association: a case report and review of the literature

<p>Abstract</p> <p>Introduction</p> <p>Autosomal dominant polycystic kidney disease is an inherited disorder that is characterized by the development and growth of cysts in the kidneys and other organs. Urinary protein excretion is usually less than 1 g/24 hours in autosomal dominant polycystic kidney disease, and an association of nephrotic syndrome with this condition is considered rare. There are only anecdotal case reports of autosomal dominant polycystic kidney disease associated with nephrotic syndrome, with focal segmental glomerulosclerosis being the most commonly reported histopathological diagnosis. Nephrotic-range proteinuria in the presence of autosomal dominant polycystic kidney disease, with or without an accompanying decline in renal function, should be investigated by open renal biopsy to exclude coexisting glomerular disease. To the best of our knowledge, this is the first case of autosomal dominant polycystic kidney disease with histologically proven diffuse proliferative glomerulonephritis presenting with nephrotic-range proteinuria. No other reports of this could be found in a global electronic search of the literature.</p> <p>Case presentation</p> <p>We report the case of a 35-year-old Indo-Aryan man with autosomal dominant polycystic kidney disease associated with nephrotic syndrome and a concomitant decline in his glomerular filtration rate. Open renal biopsy revealed diffuse proliferative glomerulonephritis. An accurate diagnosis enabled us to manage him conservatively with a successful outcome, without the use of corticosteroid which is the standard treatment and the drug most commonly used to treat nephrotic syndrome empirically.</p> <p>Conclusion</p> <p>Despite the reluctance of physicians to carry out a renal biopsy on patients with autosomal dominant polycystic kidney disease, our case supports the idea that renal biopsy is needed in patients with polycystic kidney disease with nephrotic-range proteinuria to make an accurate diagnosis. It also illustrates the importance of open renal biopsy in planning appropriate treatment for patients with autosomal dominant polycystic kidney disease with nephrotic-range proteinuria. The treatment for various histological subtypes leading to nephrotic syndrome is different, and in this modern era we should practice evidence-based medicine and should avoid empirical therapy with its associated adverse effects.</p

Vascular function assessed with cardiovascular magnetic resonance predicts survival in patients with advanced chronic kidney disease

<p>Abstract</p> <p>Background</p> <p>Increased arterial stiffness is associated with mortality in patients with chronic kidney disease. Cardiovascular magnetic resonance (CMR) permits assessment of the central arteries to measure aortic function.</p> <p>Methods</p> <p>We studied the relationship between central haemodynamics and outcome using CMR in 144 chronic kidney disease patients with estimated glomerular filtration rate <15 ml/min (110 on dialysis). Aortic distensibilty and volumetric arterial strain were calculated from cross sectional aortic volume and pulse pressure measured during the scan.</p> <p>Results</p> <p>Median follow up after the scan was 24 months. There were no significant differences in aortic distensibilty or aortic volumetric arterial strain between pre-dialysis and dialysis patients. Aortic distensibilty and volumetric arterial strain negatively correlated with age. Aortic distensibilty and volumetric arterial strain were lower in diabetics, patients with ischaemic heart disease and peripheral vascular disease. During follow up there were 20 deaths. Patients who died had lower aortic distensibilty than survivors. In a survival analysis, diabetes, systolic blood pressure and aortic distensibilty were independent predictors of mortality. There were 12 non-fatal cardiovascular events during follow up. Analysing the combined end point of death or a vascular event, diabetes, aortic distensibilty and volumetric arterial strain were predictors of events.</p> <p>Conclusion</p> <p>Deranged vascular function measured with CMR correlates with cardiovascular risk factors and predicts outcome. CMR measures of vascular function are potential targets for interventions to reduce cardiovascular risk.</p

Monitoring Insulin Aggregation via Capillary Electrophoresis

Early stages of insulin aggregation, which involve the transient formation of oligomeric aggregates, are an important aspect in the progression of Type II diabetes and in the quality control of pharmaceutical insulin production. This study is the first to utilize capillary electrophoresis (CE) with ultraviolet (UV) detection to monitor insulin oligomer formation at pH 8.0 and physiological ionic strength. The lag time to formation of the first detected species in the aggregation process was evaluated by UV-CE and thioflavin T (ThT) binding for salt concentrations from 100 mM to 250 mM. UV-CE had a significantly shorter (5–8 h) lag time than ThT binding (15–19 h). In addition, the lag time to detection of the first aggregated species via UV-CE was unaffected by salt concentration, while a trend toward an increased lag time with increased salt concentration was observed with ThT binding. This result indicates that solution ionic strength impacts early stages of aggregation and β-sheet aggregate formation differently. To observe whether CE may be applied for the analysis of biological samples containing low insulin concentrations, the limit of detection using UV and laser induced fluorescence (LIF) detection modes was determined. The limit of detection using LIF-CE, 48.4 pM, was lower than the physiological insulin concentration, verifying the utility of this technique for monitoring biological samples. LIF-CE was subsequently used to analyze the time course for fluorescein isothiocyanate (FITC)-labeled insulin oligomer formation. This study is the first to report that the FITC label prevented incorporation of insulin into oligomers, cautioning against the use of this fluorescent label as a tag for following early stages of insulin aggregation

Molecular, genetic and epigenetic pathways of peroxynitrite-induced cellular toxicity

Oxidative stress plays a key role in the pathogenesis of cancer and many metabolic diseases; therefore, an effective antioxidant therapy would be of great importance in these circumstances. Nevertheless, convincing randomized clinical trials revealed that antioxidant supplementations were not associated with significant reduction in incidence of cancer, chronic diseases and all-cause mortality. As oxidation of essential molecules continues, it turns to nitro-oxidative stress because of the involvement of nitric oxide in pathogenesis processes. Peroxynitrite damages via several distinctive mechanisms; first, it has direct toxic effects on all biomolecules and causes lipid peroxidation, protein oxidation and DNA damage. The second mechanism involves the induction of several transcription factors leading to cytokine-induced chronic inflammation. Finally, it causes epigenetic perturbations that exaggerate nuclear factor kappa-B mediated inflammatory gene expression. Lessons-learned from the treatment of several chronic disorders including pulmonary diseases suggest that, chronic inflammation and glucocorticoid resistance are regulated by prolonged peroxynitrite production